Due to the projected extensive use of long acting (-)-alpha-acetylmethadol (LAAM) in chemotherapeutic maintenance treatment programs for drug depent individuals, a thorough knowledge of the pharmacokinetics and metabolism of LAAM as well as the active metabolites of LAAM (acetylnormethadol, acetylbisnormethadol, methadol, normethadol, bisnormethadol, p-hydroxyacetylbisnormethadol) is essential for effective treatment, management and clinical safety. The major objectives of this study are: (1) determine the pharmacokinetics and metabolism of the radiolabeled metabolites of LAAM after acute and chronic administration in the monkey; (2) study the neuropharmacologic effects of LAAM and its active metabolites after acute and chronic treatment in the monkey and correlate any changes with the pharmacokinetics and metabolism of the drug; (3) correlate pharmacokinetics of LAAM and especially the active metabolites with drug-seeking behavior in the intragastric self-administering chronic monkey; and (4) determine whether ethanol interactions with LAAM or its active metabolites result in significant changes in the pharmacokinetics and biotransformation of LAAM or metabolite. Radiolabeled (3H) LAAM and 3H-acetylnormethadol are currently available in the laboratory. The other labeled metabolites will either be prepared by us or will become available through NIDA. Extraction techniques for these drugs have been developed and specificity for each is obtained through instant thin layer chromatography (ITLC). Gas-liquid chromatography, column chromatography, TLC, NMR, UV, IR and GC-mass spectroscopy will be used to determine the identify of metabolites. Intragastric and intravenous self-administration techniques for monkeys as well as neuropharmacologic instruments and methods for all currently in use in the laboratory.